The presence or absence of specific biomarkers can be predictive in the diagnosis and/or determination of a variety of conditions in an individual. As such, the accuracy of detection and quantification of a particular biomarker can be important for the correct diagnosis and treatment of an associated condition. In those cases where a biomarker is incorrectly identified in or its concentration is incorrectly determined in a biological sample, the individual can be improperly treated for a condition that is not present or can be left untreated for a condition that is present.
A variety of situations can make the detection of a biomarker problematic, both for the presence or absence of the biomarker, as well as the concentration level of the biomarker in the individual. One such situation can occur for individuals expressing autoantibodies to a biomarker in question. In such cases, the autoantibodies (AAb) can adversely affect the assay used to detect the biomarker. As one example, the measurement of thyroglobulin (Tg) is commonly used for the follow-up of patients treated for differentiated thyroid carcinoma (TC). Because thyroid tissue is the only source of Tg, total thyroidectomy and radioactive ablation should decrease serum concentrations of Tg to very low or undetectable levels. A rise of serum concentration of Tg in post-treatment patients is thus indicative of the recurrence of the TC. In a retrospective study on assessment of the utility of multiple potential biomarkers of the recurrence of TC, post-treatment Tg concentration was found to be the strongest independent predictor of the recurrence. One difficulty in using Tg as a biomarker is related to the presence of anti-Tg autoantibodies (Tg-AAb) in the blood of certain individuals. Tg antibodies were first described by Stokinger and Heidelberger in 1937, and subsequent research to date has not generated an effective commercial technique to overcome interference of Tg-AAb in testing for Tg. Current protocols to assess reliability of Tg measurements with immunoassays (IA) commonly test every specimen analyzed for Tg also for the presence of Tg-AAb.
Furthermore, it has been hypothesized that there might be a pathological and causative link between thyroid cancer coexistence and thyroid autoimmunity. Approximately 25% of patients with TC and up to 10% of individuals without TC are positive for Tg-AAb, and thus the presence of autoantibodies in samples tested for Tg by IA could cause false-negative results when epitopes used by the capture or detection antibody are occupied by the Tg-AAb. This can potentially cause misdiagnosis of the recurrence of TC.